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of glaucoma can be slowed with treatment, there is no treatment that brings
back vision in glaucoma or ischemic optic neuropathy.
4.1. Somal protection
Given that almost all optic neuropathies have in common retinal ganglion
cell axonal injury, it is reasonable to believe that therapeutic inhibition of
the molecular response of retinal ganglion cells to axonal injury would pre-
vent visual loss in such diseases. This paradigm of neuroprotection has long
been studied in neurological diseases such as stroke, with little success ( Hill,
2007 ). However, there are aspects of optic nerve diseases that make them
better candidates for neuroprotection than for other central nervous system
diseases, and in particular, the fact that soma death occurs only after several
days in axonal injury ( Schwartz, Yoles, & Levin, 1999 ). Such putative neu-
roprotective therapies would be applicable to a wide variety of diseases of
the optic nerve, independent of the mechanism by which the nerve is
damaged.
Several mechanisms may mediate retinal ganglion cell death after axonal
injury, including neurotrophin deprivation, excitotoxicity, increases in
intra-axonal Ca 2 รพ , accumulation of excess retrogradely transported macro-
molecules, and induction of p38 MAP kinase and other signaling molecules
( Cui & Harvey, 1995; Kikuchi, Tenneti, & Lipton, 2000; Kiryu-Seo et al.,
2000; Mansour-Robaey, Clarke, Wang, Bray, & Aguayo, 1994; Stys,
Ransom, Waxman, & Davis, 1990; Yoles, Muller, & Schwartz, 1997 ).
One of the most critical mechanisms is induction of c-Jun N-terminal
kinase (JNK) signaling, and in fact, elimination of JNK2 and JNK3
preserves RGCs after axonal injury ( Fernandes et al., 2012 ). Our own
group has elucidated another such signal, the generation of an
intracellular burst of superoxide that induces the apoptosis program in
axotomized retinal ganglion cells ( Kanamori, Catrinescu, Kanamori,
et al., 2010; Kanamori, Catrinescu, Mahammed, Gross, & Levin, 2010 ).
Pharmacological agents that either scavenge superoxide ( Catrinescu,
Chan, Mahammed, Gross, & Levin, 2012; Kanamori, Catrinescu,
Kanamori, et al., 2010; Kanamori, Catrinescu, Mahammed, et al., 2010 )
or reduce oxidized disulfides ( Almasieh, Lieven, Levin, & Di Polo, 2011 )
increase retinal ganglion cell survival after serum deprivation, axotomy,
or experimental glaucoma. This work and that of other groups ( Tezel,
2006 ) demonstrate that the signaling of retinal ganglion cell death in
axonal disease can be interrupted with redox-active drugs.
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